Optically-active di-[3-chloro-2-oxy-propyltrimethylammonium]-tartrate

ABSTRACT

Process for the production of optically-active di-[3-chloro-2-oxy-propyltrimethylammonium]-tartrate. Racemic 3-chloro-2-oxy-propyltrimethylammonium-chloride is converted by racemate resolution with CaCl 2 , for example, into the optically-active di-[3-chloro-2-oxy-propyltrimethylammonium]-tartrate. Such optically-active tartrate compound is dissociated into calcium tartrate and optically-active 3-chloro-2-oxy-propyltrimethylammonium-chloride, and the latter is converted with inorganic cyanides. From the product, the production of optically-active carnitine nitrile chloride can be achieved.

This is a continuation-in-part of U.S. application Ser. No. 717,547,filed on Mar. 29, 1985, now abandoned.

BACKGROUND OF THE INVENTION

1. Field of the Invention

This invention relates to optically-active tartrate compounds, tomethods of making such optically-active tartrate compounds and to theuse of such optically-active tartrate compounds for the production ofoptically-active conversion products.

2. Prior Art

Due to the slight stability of the free group of acids, the racemicresolution of free carnitine causes difficulties; so the nitrile or theamides of carnitine are predominantly used for its racemic separation.For example, East German Pat. No. 23,217 teaches converting carnitinenitrile chloride, which has been converted by treatment with silveroxide into the hydroxide or by treatment with silver carbonate into thecarbonate, with an optically-active acid into the diastereomers fromwhich the suitable diastereomer is separated. The desired carnitinederivative is isolated from the suitable diastereomer. Another path,taught by Belgian Pat. No. 660,039, starts out from carnitine amidehydrochloride, which is converted with camphoric acid in the presence ofAgNO₃ into the diastereomeric mixture. The suitable diastereomer isagain separated and analyzed.

However, the above processes have considerable disadvantages. Among suchdisadvantages is the difficulty-separable salt impurities obtained inlarge quantities, which make the dissociation of the racemate difficult.Also the numerous steps of the processes which are required to providethe carnitine amides, respectively, carnitine nitriles, accessible forthe racemate dissociation make a technical or commercial application tooexpensive with regard to costs. These difficulties are increased, sinceas a result of the use of silver salts, one must operate with theexclusion of light in order to avoid any blackening of the reactionmaterial.

BROAD DESCRIPTION OF THE INVENTION

An object of the invention is to provide the new compounddi-[3-chloro-2-oxy-propyltrimethylammonium]-tartrate. Another object ofthe invention is to provide the new compounddi-[(-)-3-chloro-2-oxy-propyltrimethylammonium]-L-(+)-tartrate(sometimes herein termed COP-tartrate). A further object of theinvention is to provide a process for the production of such newcompounds. A still further object of the invention is to provide amethod for the production of optically-active carnitine nitrile chloridefrom such new compounds. Another object of the invention is to provide aprocess which eliminates the above-described disadvantages of the priorart. Another object of the invention is to provide a process whichproduces, in a simple manner, optically-active carnitine nitrilechloride, especially (-)-carnitine nitrile chloride. Other objects andadvantage of the invention are set out herein or are obvious herefrom toone skilled in the art.

The advantages and objects of the invention are achieved by thecompounds and processes of the invention.

The invention includes optically-activedi-[3-chloro-2-oxy-propyltrimethylammonium]-tartrate. For the productionof (-)-carnitine nitrile chloride, one usesdi-[(-)-3-chloro-2-oxy-propyltrimethylammonium]-L-(+)-tartrate (COPtartrate).

The new optically-activedi-[3-chloro-2-oxy-proyltrimethylammonium]-tartrate has the formula:##STR1## The invention also includes: (a)di[(-)-3-chloro-2-oxy-propyltrimethylammonium)-L-(+)-tartrate, and

(b) di[(+)-3-chloro-2-oxy-propyltrimethylammonium)-D-(-)-tartrate.

The invention also involves producing the COP-tartrate. The COP-tartratecan be produced by several different methods. Preferably, theCOP-tartrate is produced either by conversion of racemic3-chloro-2-oxy-propyltrimethylammonium-chloride with L-(+)-tartaricacid, effectively in the presence of a trialkylamine, or by conversionof L-(+)-tartaric acid with trimethylamine and subsequent conversionwith epichlorohydrin. When proceeding according to the first method,first the racemic 3-chloro-2-oxy-propyltrimethylammonium-chloride isproduced from epichlorohydrin and trimethylamine and then the racemic3-chloro-2-oxy-propyltrimethylammonium-chloride is converted withL-(+)-tartaric acid in the presence of a trialkylamines into theCOP-tartrate.

The COP-tartrate can be dissociated from its diastereomer bycrystallization.

The trialkylamine is preferably a trialkylamine wherein each of thealkyl groups has 2 to 12 carbon atoms. While the trialkylamine can havebranched alkyl groups, preferably the trialkylamine only hasstraight-chain alkyl groups. Examples of the preferred trialkylaminesare triethylamine, tributylamine, tripropylamine, tripentylamine andtrioctylamine. Most preferably tributylamine is used.

A preferred embodiment for the production of the COP-tartrate accordingto the invention is described as follows: Starting out from 1 mole ofdextrogyric tartaric acid, effectively 1.6 to 3 moles, preferably 1.8 to2.5 moles, of tri-n-butylamine are converted with effectively 1.6 to 3moles, preferably 1.8 to 2.2 moles, of racemic3-chloro-2-oxy-propyltrimethylammonium-chloride for the production ofthe diastereomeric mixture. Preferably the conversion is operated in thepresence of water and/or a solvent which is not miscible with water,such as, methylene chloride or chloroform, and at a temperature of 0° to30° C., preferably 15° to 25° C. After separation of thetri-n-alkylamine hydrochloride by extraction with an inert solvent, suchas, methylene chloride or chloroform, the desired isomer is isolated byfractional crystallization after evaporation of the aqueous phase underreduced pressure. Effectively, the diastereomeric mixture is dissolvedin a solvent, for example, water or a lower alkanol, such as, ethanol orpreferably methanol. The crystallization of the desired isomer of theCOP-tartrate is effectively achieved by the addition of a diluent,preferably acetone.

According to another production method of the invention L-(+)-tartaricacid dissolved in water or suspended in an alcohol (lower alkanol),effectively methanol or ethanol, is placed in a vessel, subsequentlyneutralized with trimethylamine, and then thedi-[trimethylammonium]-tartrate formed as an intermediate product isconverted with epichlorohydrin at a temperature of 17° to 30° C. intothe desired COP-tartrate and its diastereomers.

A preferred embodiment for the production of the COP-tartrate accordingto the invention is as follows: Starting out with 1 mole ofL-(+)-tartaric acid, dissolved in 200 to 250 g of water or suspended ina lower (alkanol) alcohol, 1.6 to 2.5 moles, preferably 1.8 to 2.1moles, of trimethylamine is added at a temperature of 0° to 30° C. ThepH of the solution effectively is 6.5 to 7.5. Subsequently andeffectively, 1.6 to 3 moles of epichlorohydrin is added and thetemperature is held at 15° to 30° C., preferably 20° to 28° C.

Whenever the invention is operated with water, one aqueous phasedevelops. After evaporation of the water, effectively under vacuum, anoily residue results from which by treatment with organic solvent(s),effectively with methanol/acetone, the desired COP-tartrate iscrystallized out. Whenever one operates with alcohols (e.g., loweralkanol, such as methanol or ethanol), then the desired COP-tartrate isprecipitated and can be separated.

A further method for the production of COP-tartrate is where first thesilver salt of the tartaric acid is produced from silver nitrate andalkali tartrate. Then the silver tartrate is suspended in water and isconverted with racemic 3-chloro-2-oxy-propyltrimethylammonium-chloride.The desired COP-tartrate can be obtained by crystallization or can beseparated from the diastereomeric salt.

The di-[(-)-3-chloro-2-oxy-propyltrimethylammonium]-L-(+)-tartrate ofthe invention has the following properties and characteristics:

Melting point of 159° C. (after recrystallization from methanol/acetone)

[α]_(D) ²⁴ =-10.8° (c=1.04 in water)

pH of the solution (1 percent) is 7

Analysis: C, calculated is 42.39%, found is 42.36%; H, calculated is7.56%, found is 7.99%; N, calculated is 6.18%, found is 6.36%.

IR (KBr) spectrum: 3.5, 6.30, 7.20, 9.15, 10.25 micron.

For the production ofdi[(+)-3-chloro-2-oxy-propyltrimethylammonium]-D-(-)-tartrate, theracemate dissociation is conducted using D-(-)-tartaric acid. Suchproduct has the following properties and characteristics:

Melting point 159° C. (after recrystallization from methanol/acetone).

[α]_(D) ²⁴ =+10.8° (c=1.04 in water).

As a result of the process of the invention, the racemate dissociationtakes place very early in such production schemes. Thus one can workstarting with the further steps up to the carnitine nitrile chloride andcarnitine still with only one antipode, as a result of which the load ofthe further reactions by the other antipode is omitted. One ordinarilyskilled in the art could not anticipate that no further racemizationwould occur in the case of a subsequent reaction which in the end leadsto the carnitine.

The di-[(-)-3-chloro-2-oxy-propyltrimethylammonium]-L-(+)-tartrate (COPtartrate) can be converted in a simple manner into the (-)-carnitinenitrile chloride and (-)-carnitine. At the same time, one can convertthe COP-tartrate first of all with CaCl₂, followed by separating theCa-tartrate and isolating the(-)-3-chloro-2-oxy-propyltrimethylammonium-chloride. The CaCl₂ can bereplaced with, for example, 2 equivalents of HCl (aqueous) and 1equivalent of KOH (aqueous) or 1 equivalent of HCl (aqueous) and 1equivalent KCl (aqueous). The latter can be converted using an alkalicyanide into the (-)-carnitine nitrile chloride. The alkali cyanide is,for example, LiCN or KCN, but preferably is NaCN. However, one can alsocarry out the decomposition, i.e., double salt conversion, of theCOP-tartrate and the cyanide substitution reaction in one step. In thatcase, effectively an alkaline earth cyanide, preferably Ca(CN)₂ is used.At the same time the tartaric acid precipitates as the Ca-salt and the(-)-carnitine nitrile chloride can be isolated from the reactionsolution. No matter which method is used, the setting free or reactionis carried out preferably in water as a solvent.

According to another method of the invention, the optically active3-chloro-2-oxy-propyltrimethylammonium-chloride isolated from thedissociation of the COP-tartrate is converted by treatment with a strongbase, such as, an alkali hydroxide, an alkali alcoholate or an alkalitert.-butylate, into the (-)-glycidyltrimethylammonium-chloride and thelatter is converted by treatment with acetone cyanohydrin or prussicacid into the L-carnitine nitrile chloride. This method is carried outpreferably in an alcohol (lower alkanol) as a solvent at a temperaturearound ambient temperature.

The purification of the product can be achieved effectively by simplecrystallization from a solvent, such as, a lower (alkanol) alcohol.Thus, products with optical purities of 98 plus are obtained.

However, according to this process, thedi-[(+)-3-chloro-2-oxy-propyltrimethylammonium]-D-(-)-tartrate can alsobe converted into the corresponding (+)-carnitine nitrile chloride.

DETAILED DESCRIPTION OF THE INVENTION

As used herein, all parts, percentages, ratios and proportions are on aweight basis unless otherwise stated herein or otherwise obviousherefrom to one skilled in the art.

EXAMPLE 1 Production ofDi-[3-chloro-2-oxy-propyltrimethylammonium]-tartrate

While stirring, 18.54 g (100 mmole) of tri-n-butylamine was added dropby drop to 7.50 g (50 mmole) of L-(+)-tartaric acid, which was dissolvedin 50 ml of water, whereby the solution was heated to 30° C.Subsequently, 18.81 g (100 mmole) of3-chloro-2-oxy-propyltrimethylammonium chloride, which was dissolved in100 ml of water, was added to the solution. The resultant clear solutionwas extracted with 8 separate portions of 150 ml of methylene chloride.The extractions were evaporated under vacuum. 21.65 g (97.6 percentyield) of tributylamine hydrochloride was obtained. (Together, the twolast extractions only still contained 0.14 g of material.) The aqueouslayer was evaporated in a rotary evaporator until dry. 23.22 g of a veryviscous oil (102.5 percent) resulted. This was dissolved hot in 30 ml ofmethanol. It was mixed slowly with 93 ml of acetone until it becamecloudy. The latter was again made to disappear by the addition of a fewdrops of methanol. After 72 hours, the mother liquor was decanted. Thecrystal crust was washed with acetone/methanol (3:1) and was dried undervacuum. The yield was 7.20 g of crystals (31.8 percent or 63.6 percentof the theory). The crystals had a melting point of 147° to 170° C. Thecrude tartrate was dissolved in 10 g of hot methanol and gradually 45 mlof acetone were added, whereupon the crystallization immediatelystarted. The crystallization vessel was kept overnight in therefrigerator. The mother liquor was decanted off; the crystal cake waswashed with acetone and dried. 5.78 g of crystals, corresponding to 51percent of the theory, were obtained. The crystals had a melting pointof 150° to 152° C. and a [α]_(D) ²⁴ of -7.5° (c=1.04 in water). Thetributylamine was recovered from the methylene chloride residue (rawtributylamine hydrochloride) with a yield of 96 percent by placing theresidue in a solution of methylene chloride, shaking the solution with1N of caustic soda solution and removing the solvent under vacuum.

EXAMPLE 2 Production ofDi-[(-)-3-chloro-2-oxy-propyltrimethylammonium]-L-(+)-tartrate

To 18.75 g (125 mmole) of L-(+)-tartaric acid, which was dissolved in 30ml of water, 39 ml (259 mmole) of trimethylamine was added dropwisewithin 10 minutes while stirring. The temperature was kept at 30° C. ThepH of the solution was 7. Subsequently, the solution was cooled to 15°C. and 23.15 g (250 mmole) of epichlorohydrin was added dropwise whilestirring. The reaction temperature was kept at 25° C. and the stirringwas continued until the mixture consisted only of a liquid phase. Aftercompleting the reaction, the water was evaporated under vacuum (Rotavap)at 40° C. 59.5 g of a viscous oil resulted. This residue was dissolvedin 40 ml of hot methanol and gradually 135 ml of acetone were addeduntil cloudiness occurred. After letting the solution stand for 72hours, at ambient temperature, the mother liquor was decanted off andthe crystals were washed with acetone/methanol (4:1) and dried undervacuum. 4.75 g of plate-shaped crystals resulted. The yield of crystalswas 16.8 percent of the theory. The crystals had a melting point of 150°to 152° C. and a [α]_(D) ²⁴ of -8.1° (c=1 in water).

EXAMPLE 3 Production ofDi-[(-)-3-chloro-2-oxy-propyltrimethylammonium]-L-(+)-tartrate

150 g (1 mole) of L-(+)-tartaric acid was suspended in 200 g of methanoland, at a temperature of 20° C., 106.2 g (1.8 mole) of trimethylamineand 250 g of ethanol were added within 1 hour. The temperature was keptat 20° C. The tartaric acid was dissolved while formingdi-trimethylammonium-L-(+)-tartrate. Subsequently, 166.5 g (1.8 mole) ofepichlorohydrin was added and the temperature was kept at 20° C. Thestirring continued for 2 days while maintaining such temperature. Theemerging crystals were filtered off, washed with acetone/methanol (4:1)and dried under vacuum. The product was obtained in a yield of 38.9percent (77.8 percent of the theory). The product had a melting point of157° to 158° C. and had a [α]_(D) ²⁴ of -9.1° (c=1 in water).

EXAMPLE 4 Production ofDi-[(-)-3-chloro-2-oxy-propyltrimethylammonium]-D-(-)-tartrate

46.25 g (127 mmole) of di-silver-L-(+)-tartrate was suspended in 350 mlof water and was mixed with a solution of3-chloro-2-oxy-propyltrimethylammonium chloride, which was dissolved inwater. The suspension was stirred for 4 hours. The silver chlorideformed was filtered off and (for the purpose of quick drying) was washedwith methanol and ether and then dried. 36.21 g of silver chloride (99.5percent of the theory) resulted. The filtrate was completely evaporatedin a rotary evaporator. The residue weighed 61.43 g (theory: 57.58 g)after drying in an oil vacuum (5 hours at room temperature). The crystalcake was dissolved in 80 ml of hot methanol and 260 ml of acetone wasadded gradually to the hot solution. The turbidity which developed wasmade to disappear by the addition of 2 ml of methanol. The vessel wasclosed and allowed to cool. After a few minutes, crystallization startedat the wall of the vessel. After 48 hours, the vessel and its contentswere still kept for 3 hours in a refrigerator (+4° C.). The motherliquor was decanted from the crystal crust. The crystals were washedwith approximately 20 ml of acetone/methanol (1:5) and a little acetone,and were then dried under vacuum. 19.33 g of crystal clusters resultedwhich had a melting point o 159° C. (after crystallization fromacetone/methanol) and a [α]_(D) ²⁴ of +10.8° (c=1.04 in water).

EXAMPLE 5 Production of(-)-3-chloro-2-oxy-propyltrimethylammonium-chloride

4.50 g (40.5 mmole) of calcium chloride, which was dissolved in 15 ml ofwater, was added dropwise to 18.35 g (40.5 mmole) of tartrate (accordingto Example 1), which was dissolved in 65 ml of water while rotating thevessel. The calcium tartrate immediately crystallically precipitated.After 5 minutes, the suspension was cooled in an ice bath (the solutionhad a pH of 7) and the calcium tartrate was filtered off. After washingwith methanol and drying in air, the material weighed 10.08 g (theoryfor the tetrahydrate: 10.54 g, yield 95.6 percent). The filtrate (andwash-methanol) was evaporated at a 50° C. bath temperature in a rotaryevaporator. The solid residue, which weighed 17.0 g (theory: 15.24 g),was digested at 70° C. with 25 ml of absolute ethanol. The suspensionwas cooled in an ice bath and the crystals were filtered. After washingwith ethanol/acetone (1:1) and acetone, the material was dried in air.The yield was 10.24 g of colorless crystals (67.2 percent of thetheory). The colorless crystals had a melting point of 214° C. and a[α]_(D) ²⁴ of -28.76° (c=0.97 in water).

EXAMPLE 6 Production of (-)-carnitine nitrile chloride

8.61 g (45.76 mmole) of the product produced according to Example 5 in 9ml of methanol and 1 ml of water was mixed dropwise in a bath (50° to55° C.) within 3 minutes with 3.43 g (47.0 mmole) of sodium cyanide in 8ml of water. The reaction solution, which immediately became turbid, wasleft in the bath for 20 minutes (pH 8 to 9) and was then adjusted to pH5 with 5.5N hydrochloric acid (3.0 ml of acid was needed). After coolingof the composition with a bath (-100° C.) for a few minutes, the saltobtained was filtered off, washed with ice-cold methanol and dried. 1.89g of salt was obtained. The filtrate was concentrated under vacuum at a40° C. bath temperature. The residue, a yellowish solid mass (10.6 g),was taken in 23 g of hot methanol. The warm solution (40° C.) wasfiltered (removal of 0.60 g of insoluble material). The filtrate wasagain filtered (separation of about 0.1 g of salt), heated untilsettling (weight of the solution, 24 g) and cooled to 0° C. Theseparated crystals were subjected to suction, washed with a littlemethanol (-10° C.) and ether, and dried. The yield was 4.62 g of almostcolorless crystals (56.5 percent of the theory). The crystals had amelting point of 244° C. and a [α]_(D) ²⁴ of -28.30° (c=1.06 in water).The product contained starting material (tlc). After being twicerecrystallized from ethanol (95 percent), long needles were obtainedwhich had a melting point of 256° C. and a [α]_(D) ²⁴ of -25.9° (c=1.05in water).

EXAMPLE 7 Production of (-)-glycidyltrimethylammoniumchloride((-)-N,N,N-trimethyl-oxiranemethane amine)

At ambient temperature while stirring, a solution of 2.05 g NaOH (98percent 50 mmole) in 45 ml of methanol was added dropwise to 9.5 g (50mmole) of (-)-3-chloro-2-oxypropyltrimethylammonium-chloride [99.1percent [α]_(D) ²⁴ =-29.5° (c=1, H₂ O), melting point 212° to 214° C.]dissolved in 35 ml of methanol. The mixture was stirred for 3 hours. Theprecipitated NaCl (2.6 g, 89 percent was filtered off and washed twicewith portions of 5 ml of ethanol. The filtrate and the wash ethanol wereevaporated. The raw product (8.95 g, 117 percent) was absorbed in 50 mlof chloroform, whereupon, after shaking, the product gradually dissolvedexcept for some NaCl. This insoluble NaCl (0.60 g, 20 percent) wasfiltered off. Afer evaporating off the CHCl₃, 7.6 g (99.3 percent)(-)-glycidyltrimethylammoniumchloride was obtained. The product did notcontain any starting material (tlc). The product had a melting point of121° to 123.5° C. and a [α]_(D) ²⁴ of -27.0° (c=1 in water). Analysis ofthe product showed:

IR (KBr): 3440s, 3030w, 2980w, 2940w, 1630m, 1485s, 1420w, 1270w, 1150w,1100w, 980m, 935s, 900m, 870m 805w 770w.

¹ H-NMR (300 MHz, d₆ -DMSO): 2,69 (dd, 1H, J=5 and 3 Hz, H-C(3)); 2,93(dd, 1H, J=5 and 5 Hz, H-C(3)); 3,22 (dd, 1H, J=13 and 8 Hz, H-C(1));3,23 (s, 9H, --N(CH₃)₃); 3,57 (dddd, 1H, J=8/5/3 and 3 Hz, H-C(2)); 4,04(dd, 1H, J=13 and 3 Hz, H-C(1)).

EXAMPLE 8 Production of (-)-glycidyltrimethylammonium-chloride((-n)-N,N,N-trimethyl-oxirane methane amine

At ambient temperature while stirring, a solution of 5.8 g KOtBu (97percent, 50 mmole) in 20 ml of methanol was added dropwise to 9.5 g (50mmole) of (-)-3-chloro-2-oxy-propyltrimethylammonium-chloride [99.1percent [α]_(D) ²⁴ =-29.5° (c=1, water), melting point of 212° to 214°C.], which was dissolved in 35 ml of methanol. The mixture was stirredfor 3 hours. The precipitated KCl (3.95 g, 105 percent was filtered offand washed twice with portions of 5 ml of ethanol. The filtrate and thewash-ethanol were evaporated. The raw product (9.15 g, 119 percent) wastaken in 50 ml of chloroform, whereupon, after shaking, the productgradually dissolved except for some KCl. This insoluble KCl (0.05 g,traces) was filtered off. After evaporating off the CHCl₃, 7.5 g (98percent) (-)-glycidyltrimethylammonium-chloride was obtained. Theproduct did not contain any starting material (tlc). The product had amelting point of 119° to 121° C. and a [α]_(D) ²⁴ of -27.1° (c=1 inwater).

EXAMPLE 9 Production of L-carnitine Nitrile Chloride

4.35 g of acetone cyanohydrin (98 percent, 50 mmole) and 7.9 g (50mmole) of (-)-glycidyltrimethylammonium-chloride were added to 10 ml ofMeOH (i.e., methanol). The mixture was stirred at 20° to 25° C. untilall of its solid components were dissolved. After that the solution washeated within half hour to 45° C. and stirring at this temperature wascontinued for 4 hours (thin layer chromatogram). The product began toprecipiate after one half hour at 50° C. The mixture was cooled to 20°C. The resultant white crystals were filtered, washed three times, eachtime with 6 ml of acetone, and dried. The yield was 7.5 g (81.6 percentof the theory) of such white crystals. The white crystals had a meltingpoint of 246° C. (composition) and a [α]_(D) ²⁴ of -25.6° (c=1 inwater). The product was 97.3 percent (HPLC) and contained 2.4 percent of(-)-glycidyltrimethylammonium-chloride. After recrystallization fromethanol (95 percent), long needles were obtained. The long needles had amelting point of 256° C. (decomposition) and a [α]_(D) ²⁴ of -25.8° (c=1in water).

EXAMPLE 10 Production of (-)-3-chloro-2-oxy propyltrimethylammoniumchloride

228.3 g (0.5 mol) of di[(-)-3-chloro-2-oxy-propyltrimethylammonium]-L(+)tartrate was dissolved in a mixture of 315 ml of H₂ O and 135 ml ofethanol at room temperature. Within a 2-minute period, 38.2 g (0.5 mol)of solid KCl was added to the stirred solution. The KCl dissolved within2 to 3 minutes. 49.4 g of HCl (37 percent in H₂ O; 0.5 mol) was addeddropwise to the solution within 10 minutes. During this addition, theK,H-tartrate precipitated and the pH dropped to 3.2. The reactionmixture was stirred for 1 hour at room temperature, cooled to 4° C. andthe K,H-tartrate was filtered by means of suction, washed withalcohol/water and air dried. The yield was 94.2 g [100.1 percent,[α]_(D) ²⁰ =31.5° (c=1.1M NaOH)]. The filtrate (and wash solvent) wasevaporated in a rotary evaporator at a bath temperature of 50° C. untilthe (-)-3-chloro-2-oxy-propyltrimethylammonium chloride began toprecipitate. Then the mixture was cooled to room temperature. Thecrystals of (-)-3-chloro-2-oxy-propyltrimethylammonium chloride werefiltered by suction, washed with ethanol/acetone and dried. The yieldwas 88.5 g [(47.0 percent, [α]_(D) ²⁴ =-29.7° (c=1, H₂ O)]. The motherliquor and the wash solvent were evaporated to dryness. The residue wasdigested with 160 ml of absolute ethanol at 70° C. The suspension wascooled in an ice bath. The crystals of(-)-3-chloro-2-oxy-propyltrimethylammonium chloride were filtered bymeans of suction, washed with ethanol/acetone and dried. The yield was83.6 g [44.5 percent, [α]_(D) ²⁴ =29.3° (c=1, H₂ O)].

EXAMPLE 11 Production of (-)-3-chloro-2-oxy-propyl trimethylammoniumchloride

228.3 g (0.5 mol) ofdi-[(-)-3-chloro-2-oxy-propyltrimethylammonium]-L-(+) tartrate wasdissolved in a mixture of 315 ml of H₂ O and 135 ml of ethanol at roomtemperature. 88.9 g of HCl (37 percent in H₂ O; 0.9 mol) was addeddropwise to the stirred mixture within 8 minutes and then a solution of28.1 of KOH (0.5 mol) was added dropwise in 30 ml of H₂ O within 10minutes. the K,H-tartrate immediately precipitated crystalline. The pHwas brought to 3.2 to 3.5 with 9.8 g HCl (37 percent in H₂ O; 0.1 mol).The reaction mixture was stirred for 1 hour at room temperature, cooledto 4° C. and the K,H-tartrate was filtered by means of suction, washedwith ethanol/H₂ O and air dried. The yield was 94.6 g [100.8 percent,[α]_(D) ²⁰ =+31.3° (c=1.1M NaOH)]. The(-)-3-chloro-2-oxy-propyltrimethylammonium chloride was isolated as inExample 1.

EXAMPLE 12 Production of (-)-3-chloro-2-oxy-propyltrimethylammoniumchloride

The K,H-tartrate was prepared and filtered from 228.3 g (0.5 mol) ofdi-[(-)-3-chloro-2-oxypropyltrimethylammonium]-L-(+) tartrate accordingto Example 10. Then the filtrate and the wash solvent were evaporated ina rotary evaporator to a weight of 350 g. 600 ml of toluene was addedand the residual water was distilled off azeotropically. Afterdistillation of about 150 g of water, the (31)-3-chloro-2-oxy-propyltrimethylammonium chloride crystallized out. Theheterogeneous mixture was cooled to room temperature and filtered bymeans of suction. The crystals were washed twice, each time with 25 mlof ethanol/acetone 1:1 and dried. The yield was 17.65 g (93.6 percent)of (-)-3-chloro-2-oxy-propyltrimethylammonium chloride. Also, [α]_(D) ²⁴=-29.8° (c=1.0 H₂ O).

What is claimed is:
 1. Process for producing optically-active carnitinenitrile chloride from optically-activedi-(3-chloro-2-oxy-propyltrimethylammonium)-tartrate comprising (a)dissociating the di-(3-chloro-2-oxy-propyltrimethylammonium)-tartrate(i) with CaCl₂ into Ca-tartrate and optically active3-chloro-2-oxy-propyltrimethylammonium chloride, or (ii) with twoequivalents of HCl and one equivalent of KOH or one equivalent of HCland one equivalent KCl into K-H-tartrate and optically-active3-chloro-2-oxy-propyltrimethylammonium chloride, and (b) converting theoptically-active 3-chloro-2-oxy-propyltrimethylammonium chloride with aninorganic cyanide into the optically-active carnitine nitrile chloride.2. Process as claimed in claim 1 wherein the inorganic cyanide is Li CN,KCN or Na CN.
 3. Process for producing (-)-carnitine nitrile chloridefrom di-[(-)-3-chloro-2-oxy-propyltrimethylammonium]-L-(+)-tartratecomprising (a) dissociating thedi-[(-)-3-chloro-2-oxy-propyltrimethylammonium]-L-(+)-tartrate (i) withCaCl₂ into Ca-tartrate and (-)-3-chloro-2-oxy-propyltrimethylammoniumchloride, or (ii) with two equivalents of HCl and one equivalent of KOHor one equivalent of HCl and one equivalent of KCl into K-H-tartrate and(-)-3-chloro-2-oxy-propyltrimethylammonium chloride, and (b) convertingthe (31 )-3-chloro-2-oxy-propyltrimethylammonium chloride with aninorganic cyanide into the optically-active carnitine nitrile chloride.4. Process as claimed in claim 3 wherein the inorganic cyanide is LiCN,KCN, or NaCN.